Ondansetron hydrochloride is a competitive serotonin 5-HT3 receptor antagonist used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery.
The chemical name of Ondansetron is (RS)-9-methyl-3-[(2-methyl-1H-imidazol-1-yl) methyl]-2,3-dihydro-1H-carbazol-4(9H)-one and its HCl salt is structurally represented as

Ondansetron hydrochloride is a white to off-white powder that is soluble in water and normal saline, having intensely bitter taste.
Ondansetron hydrochloride is commercially available as the conventional oral solid dosage forms in the strengths of 4 mg & 8 mg of ODT & 5 mL of ORAL SOLUTION is marketed with the Brand name ZOFRAN in the USA. 4-mg and 8-mg doses of either ZOFRAN oral solution or ZOFRAN ODT Orally disintegrating tablets are bioequivalent to corresponding dose of ZOFRAN tablets and may be used interchangeably.
Ondansetron hydrochloride films are commercially available as ZUPLENZ (ondansetron) oral soluble film approved in two strengths. The thin white opaque films are rectangularly shaped strips with a printed identifier in black ink of “4 mg” for ZUPLENZ 4 mg or “8 mg” for ZUPLENZ 8 mg. Each 8-mg ZUPLENZ oral soluble film for oral administration contains 8 mg ondansetron base. Each ZUPLENZ oral soluble film also contains the inactive ingredients butylated hydroxytoluene, calcium carbonate, colloidal silicon dioxide, erythritol, hydroxypropyl methylcellulose, monoammonium glycyrrhizinate, peppermint flavor, polyethylene oxide, sodium bicarbonate, sucralose, titanium dioxide and xanthan gum.
Christian et al in U.S. Pat. No. 8,580,830 provides a non-mucoadhesive orally disintegrating film dosage forms that mimic the pharmacokinetic profile of orally administered drug products such as tablets, capsules, liquid suspensions, and orally dissolving/dispersing tablet (ODT).
Christian et al provides a non-mucoadhesive orally disintegrating film comprising ondansetron or a pharmaceutically acceptable salt thereof in combination with a hydrophilic binder and a water-soluble diluent, able to disintegrate upon contact with saliva in the buccal cavity within about sixty seconds. Example 1 formulation comprise of ondansetron, polyvinylalcohol, polyethylene glycol, glycerol anhydrous, rice starch, acesulfame K, titanium dioxide, menthol and polysorbate.
Gary et al in US20100297232 relates to an ondansetron film compositions relating to a self-supporting film dosage composition comprising: a polymer mixture of PEO and HPMC, Xanthan gum as additive, an active component, at least one slow-dissolving alkaline component like calcium carbonate and at least one fast-dissolving alkaline component like sodium bicarbonate.
Robert et al in WO2006031209 relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, these films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. The films contain a polymer component, which includes polyethylene oxide optionally blended with hydrophilic cellulosic polymers. These films also contain a pharmaceutical and/or cosmetic active agent with no more than a 10% variance of the active agent pharmaceutical and/or cosmetic active agent per unit area of the film. Robert et al. reference provides a rapid-dissolve film product comprising: at least one water-soluble polymer comprising polyethylene oxide alone or in combination with a hydrophilic cellulosic polymer, wherein said film product is free of added plasticizers.
Robert et al refers to a rapid-dissolve film product which is free of added plasticizers. The said prior art reference teaches different ratios of combination of polyethylene oxide with a hydrophilic cellulosic polymer, and use of surfactants and antifoaming agents as essential components for making film for achieving content uniformity of the pharmaceutical and/or cosmetic active agents in the film.
Horst et al in US20030053962 refers to a breath freshening film comprising: at least one hydroxypropyl cellulose; at least one modified starch; and at least one flavor ingredient. An improved rapidly disintegrating flavored film that quickly and completely disintegrates upon contact with mucosal tissue in the oral cavity of a human includes hydroxypropyl cellulose, a modified starch and a flavor ingredient. The flavored films of this invention completely disintegrate upon contact with the mucosal tissue in less than a minute, and often in less than 30 seconds, whereas previously known flavored films typically do not complete dissolve, or do not dissolve as rapidly, upon contact with mucosal tissue in the oral cavity of a human. The flavored films of this invention may be advantageously employed as breath freshening films, and in food items to impart flavor and, optionally, to impart functional qualities to the food item. However, these films do not provide a clean mouth sensation due to the fact that the hydrocolloids tend to gel on contact with saliva. One solution to the aforesaid drawbacks are provided in WO2003011259 from which is noted that, to obtain properties equivalent to those of pullulan, it is crucial that maltodextrin, smaller quantities of hydrocolloid and, additionally, inert filler are present simultaneously in the filmogenic composition.
Francesco et al in WO2005039543 relates to rapidly dissolving self-supporting films for food or pharmaceutical use comprising: a) a filmogenic substance consisting of a maltodextrin; b) a plasticiser; c) an active principle for food or pharmaceutical use, characterised in that said films are free of hydrocolloids.
Petra et al in US20080213343 relates to Film-form preparation comprising one or more film formers, one or more gel formers and one or more active ingredients selected from the group consisting of anti-emetics and anti-migraine agents, wherein said preparation is single-layered and are free of surfactants, effervescent additives and taste maskers.
Petra et al in US20080213343 relates to one or more film former(s) from the following group:                sugar, sugar alcohols and derivatives thereof, especially saccharose, sorbitol, mannitol, xylitol, glucose, fructose, lactose and galactose, low molecular weight organic acids, especially citric acid, succinic acid, malic acid and adipic acid,        polyethylene glycol, polyethylene glycol dioleate, 1,3-butanediol, propylene glycol, glycerol, isopropyl palmitate, dibutyl sebacate, paraffin oil and castor oil,        ethylcellulose, cellulose acetate,        cellulose phthalate,and mixtures of such film formers.        
Petra et al in US20080213343 relates to at least one gel former from the following group can be provided:                polymeric carbohydrates, especially cellulose and derivatives thereof, preferably hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), starch and derivatives thereof, agar-agar, alginic acid, arabinogalactan, galactomannan, carrageenan, dextran, tragacanth and gum of vegetable origin,        synthetic polymers that are soluble or swellable in water, especially polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid and polyacrylamide,        polypeptides, especially gelatin, albumin and collagen, andmixtures of such gel formers.        
Rajesh et al in WO2012/053006 relates to an oral fast dispersing or dissolving film for delivery of active comprising therapeutically effective amount of an active pharmaceutical agent, at least one water soluble polymer as essential polymer base in combination with film forming polymer in a ratio of about 25:1 to about 250:1. The prior art reference discloses an oral fast dispersing or dissolving film comprising a. about 2-40% of ondansetron, b. about 0.1-2% of pectin, c. about 10-50% of hydroxypropyl methyl cellulose and d. about 10-50% of maltodextrin.
Each of the films of the representative prior art patents, discussed briefly above have certain disadvantages as compared to the components of the films and methods of the present invention. The following disadvantages can be observed like—                a) Robert et al refers to a rapid-dissolve film product made of polyethylene oxide with a hydrophilic cellulosic polymer which is free of added plasticizers. However, the use of surfactants and antifoaming agents were inevitable components for making films.        b) Petra et al in US20080213343 relates to Antiemetic Film preparations comprising one or more film formers, one or more gel formers wherein said preparation is single-layered and are free of taste maskers. The undesired taste of the drug would be unacceptable and may not provide patient compliance.        c) Francesco et al in WO2005039543 relates to rapidly dissolving self-supporting films for food or pharmaceutical use comprising: a) a filmogenic substance consisting of a maltodextrin; b) a plasticiser; c) an active principle for food or pharmaceutical use, characterised in that said films are free of hydrocolloids. The high concentrations of maltodextrin can pose problems in making film preparations.        d) Gary et al in US20100297232 relates to an ondansetron film compositions relating to a self-supporting film dosage composition comprising: a polymer mixture of PEO and HPMC, Xanthan gum, calcium carbonate and sodium bicarbonate. The presence of slow-dissolving alkaline component like calcium carbonate and fast-dissolving alkaline component like sodium bicarbonate and also pose several formulation challenges in film preparation and would greatly affect the product characteristics.        
Despite the wide existence of teachings for making ondansetron oral films in the prior art, however, still there is a need for providing an economically feasible, improved, stable oral film that is easy to make and that can accommodate drugs like ondansetron.
Surprisingly, an improved pharmaceutical Film Compositions of Ondansetron or a salt thereof, methods of formulating the Film Compositions of Ondansetron or a salt thereof, and are comparable to commercially available Ondansetron solid oral dosage foal's.